tbuckley/cabot-search huggingface dataset:
A multicenter, non-randomized, controlled trial to evaluate the efficacy of surgery versus radiofrequency ablation for small hepatocellular carcinoma (SURF-Cohort Trial): Analysis of overall survival.
Authors: Tatsuya Yamashita, Yoshikuni Kawaguchi, Shuichi Kaneko, Tadatoshi Takayama, Namiki Izumi, Naoki Yamanaka, Masatoshi Kudo, Mitsuo Shimada, Masafumi Inomata, Hideo Baba, Kazuhiko Koike, Masao Omata, Masatoshi Makuuchi, Yutaka Matsuyama, Norihiro Kokudo, Kiyoshi Hasegawa
Journal: Journal of Clinical Oncology (2022)

4095 Background: We conducted a multicenter prospective study (SURF trial) to compare the efficacy of surgery vs. radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC). SURF trial consisted of a randomized controlled trial (SURF-RCT) and a non-randomized prospective observational study (SURF-Cohort), including patients who did not consent to randomization. The initial report of the SURF-Cohort trial showed that recurrence-free survival (RFS) did not differ significantly between patients undergoing surgery and RFA. The focus of the present report was to assess the efficacy for overall survival (OS). Methods: The SURF-Cohort trial was a prospective multicenter study conducted in 49 institutions in Japan. Patients (aged between 29 and 79 years) with Child-Pugh scores ≤ 7, largest HCC diameter ≤ 3 cm, and ≤ 3 HCC nodules were considered eligible. Before the enrollment, both liver surgeons and hepatologists who perform RFA confirm that all the patients can be treated using both surgery and RFA. The co-primary endpoints were RFS and OS. OS was assessed at 5 years after the last accrual as per the protocol. Inverse probability of treatment weighted (IPTW) analysis was used to balance the characteristics of the groups. This trial is registered in UMIN000001796. Results: During 2009–2015, 782 patients were enrolled. After excluding ineligible patients, the surgery and RFA groups included 382 and 371 patients, respectively. In the surgery group, median platelet count (13.7x10 4 vs. 11.5x10 4 , P&lt; 0.01) was significantly greater, and the median largest HCC diameter was significantly greater (2.0 cm vs. 1.8 cm, P&lt; 0.01) than in the RFA group. The median (range) follow-up period was 6.8 years in the surgery group and 6.7 years in the RFA group. The IPTW-adjusted OS did not differ significantly between the surgery and RFA groups: the 5-year OS, 79.7% vs. 79.3%; HR 0.98; 95% CI 0.75–1.30; P= 0.906. The analysis after long-term follow-up in the current report showed that RFS was not significantly different between the surgery and RFA groups: the 5-year RFS, 44.6% vs. 39.3%; HR 0.86; 95% CI 0.71–1.06; P= 0.155. Conclusions: SURF-Cohort trial revealed that OS and RFS after the IPTW adjustment were not significantly different between patients undergoing surgery and RFA for early stage HCC (≤ 3 cm and 3 nodules). Clinical trial information: UMIN000001796.
Disparities in pegasparagase-induced toxicity in Hispanic patients with acute lymphoblastic leukemia.
Authors: Alexis Chen Boulter, Justin Lin Sovich, Radhika Kainthla, Navid Sadeghi, Amy Little Jones
Journal: Journal of Clinical Oncology (2022)

e18590 Background: Hispanic individuals experience the highest incidence of acute lymphoblastic leukemia of any racial or ethnic group in the United States. While Hispanic individuals are known to have disproportionately increased mortality and higher therapy-related toxicity rates in ALL, there is a paucity of data regarding ethnic differences in rates of toxicity related to pegasparagase, a backbone of ALL treatment regimens. In our safety-net hospital system, we sought to evaluate disparities in rates of pegasparagase-induced hepatotoxicity between Hispanic and non-Hispanic patients. Methods: Pegasparagase infusions administered in adult ALL patients from 2011-2020 at Parkland Memorial Hospital in Dallas, Texas, were identified using the electronic medical record. Retrospective review of demographic, clinical, and socioeconomic data was conducted. For each infusion, dosing, timing, transaminase trends, and toxicity data were gathered. Statistical analysis was completed with Excel Analysis ToolPak and R Statistical Software. Accounting for baseline characteristics (age, BMI, sex, metabolic comorbidities, and baseline hepatic function), multiple linear regression models were constructed for peak transaminase and bilirubin levels. ANOVA testing, adjusted R 2 values, and AIC were utilized to compare the contribution of race, ethnicity, and socioeconomic variables to modeling. Results: 47 individual patients received pegasparagase during the study period with 196 infusions evaluated. The mean age was 30 years, 29% were female and 73.4% white Hispanic. There were 64 grade 3-4 pegasparagase-related toxicities (54 hepatotoxicity, 4 pancreatitis, 6 thrombosis). 83.3% of grade 3-4 hepatotoxicity events were in Hispanic patients, and 16.7% in non-Hispanics. The median time from infusion to grade 3-4 toxicity was 18 days. Hispanic ethnicity was significantly associated with severe hepatoxicity (P = 0.0004). An interaction was identified with insurance status and primary language which significantly strengthened the impact of ethnicity and race on hepatotoxicity severity (P = 0.005, P = 0.02). Conclusions: In our safety-net population, Hispanic ethnicity was associated with significantly higher grades of hepatotoxicity when compared to non-Hispanic patients. Uninsured status and primary Spanish language use were not only independently associated with increased toxicity but also strengthened the effect of Hispanic ethnicity on the severity of liver dysfunction related to pegasparagase. These findings propose that Hispanic patients may benefit from closer monitoring during treatment with pegasparagase-containing regimens and highlight the need for further studies to improve risk-stratification of Hispanic patients when selecting ALL therapy.
Precision Promise (PrP): An adaptive, multi-arm registration trial in metastatic pancreatic ductal adenocarcinoma (PDAC).
Authors: Vincent J. Picozzi, Anne-Marie Duliege, Eric Andrew Collisson, Anirban Maitra, Manuel Hidalgo, Andrew Eugene Hendifar, Gregory Lawrence Beatty, Sudheer Doss, Lynn McCormick Matrisian, Pamela S Herena, Julie Fleshman, Michelle A. Detry, Donald A. Berry, Diane M. Simeone
Journal: Journal of Clinical Oncology (2022)

TPS4188 Background: The success rate of drug development in PDAC is disappointingly low.PrP is a transformative, adaptive platform clinical trial designed to continuously evaluate many novel therapeutic options while increasing the probability that patients (pts) are randomized to effective experimental therapies. It cultivates enhanced cooperation among groups representing pts advocacy, pharmaceutical companies, academia, and the FDA. This patient-centric study aims to become the largest Phase 3 registrational study in PDAC and represents a fundamental shift in drug development for PDAC in the United States (US). Methods: PrP (NCT04229004) is a platform clinical trial sponsored by the Pancreatic Cancer Action Network (PanCAN), developed based on the FDA 2020 guidance document regarding "complex innovative designs" in registration trials https://www.fda.gov/media/130897/download . It utilizes adaptive randomization and other Bayesian statistical innovations provided by Berry Consultants LLC, including the “time machine” which uses all previously randomized controls for each arm, suitably adjusted for line of therapy and the time period of the arm. Focused on 1 st and 2 nd line treatment of mPDAC, PrP uses an adaptive platform design with randomization to one of 2 control arms (gemcitabine + nab-paclitaxel (GA) or mFOLFIRINOX, 30% of pts) or experimental therapy (70% of pts). Candidate experimental arms are reviewed by an Arm Selection Committee based on validity of the treatment target and strength of the pre-clinical and clinical data. The primary endpoint is overall survival (OS). Pts undergo pre- and on-treatment biopsies with state-of-the-art genomic, transcriptomic, and immune analysis, along with a serial collection of blood-based research samples. Pts are managed using novel supportive care techniques; PrP contains 3 sub-protocols evaluating quality of life, sarcopenia, and actigraphy. PrP launched in 2020 and has enrolled &gt; 130 pts; 30 US sites have been selected with 17 currently active. Current experimental arms include: (i) GA + Pamrevlumab, an anti-CTGF Ab, (ii) Racemetyrosine monotherapy, a cancer metabolism-based therapy (for follow-up of patients) and (iii) an immuno-oncology arm in activation. Other arms are in the planning stages. Compared to traditional designs, PrP offers several advantages: multiple investigational treatments evaluated in parallel over time; ̃175 pts per experimental arm required to initiate a regulatory registration; and continuous learning from every patient, resulting in significant savings of time and resources. PrP has created an entirely new learning environment for accelerating drug development in PDAC. Clinical trial information: NCT04229004.
Improving care coordination for adolescents and young adults with cancer.
Authors: Emily Ruth Haines, Lauren Lux, Melissa Matson, Catherine Swift, Daniel Kleissler, Andrew Brian Smitherman, Sarah Birken
Journal: Journal of Clinical Oncology (2022)

TPS1598 Background: In the US, many of the 90,000 adolescents and young adults (AYAs) (i.e., individuals ages 15-39) diagnosed with cancer each year do not receive services to address the range of needs they experience during cancer treatment. AYAs’ unmet needs are associated with higher distress, poorer health-related quality of life, and higher physical symptom burden. However, AYAs often do not use services available to them through their cancer programs, even when they face no access issues (e.g., cost, insurance status, local service capacity). AYAs report barriers to service use including lack of awareness, challenges navigating large volumes of information and complex health systems, and hesitance to broach needs with providers without prompting. To facilitate a systematic and patient-centered approach to addressing AYAs' unmet needs, we leveraged user-centered design to develop the AYA Needs Assessment &amp; Service Bridge (NA-SB). NA-SB includes a patient-reported outcome measure assessing AYAs’ physical, psychosocial, and practical needs, and a collection of referral pathways for connecting AYAs to services based on the needs they report. In this feasibility pilot study, we are evaluating the implementation of NA-SB in the University of North Carolina Lineberger Comprehensive Cancer Center (UNC) AYA Cancer Program. Methods: Eligible participants include AYAs ages 18-39 currently undergoing cancer treatment at UNC (n = 25-50). The needs assessment portion of NA-SB is administered electronically through REDCap during routine clinical encounters with the AYA team. After an AYA completes the needs assessment, an AYA provider (i.e., social worker/nurse practitioner) reviews their responses and initiates referral pathways. Six weeks following their completion of the needs assessment, AYAs complete a survey assessing their perceptions of (1) the usability of the NA-SB needs assessment, (2) the feasibility, acceptability, and appropriateness of implementing NA-SB, and (3) the extent to which their needs have been met. We are also assessing participating providers’ perceptions of NA-SB’s implementation through periodic check-in calls. Results: We will report descriptive statistics on participant demographics, needs reported, and quantitative outcomes. We will analyze data from provider check-in calls inductively to further elaborate on implementation experiences and determinants. Conclusion: By harnessing patient-reported data to facilitate care coordination for AYAs, NA-SB has the potential to improve processes of care and subsequent outcomes for AYAs, an underserved and understudied population. This pilot study represents a critical first step towards translating NA-SB into routine cancer care for AYAs. Clinical trial information: NCT04586127.
Effectiveness of COVID -19 vaccine on cancer patients in one Latin American country: A follow-up of ACHOC-C19 study.
Authors: Aylen Vanessa Ospina Serrano, Ricardo Elias Bruges Maya, Pedro Ramos, Ivan Triana, Sandra Aruachan, Alicia Quiroga, Giovanna Patricia Rivas Tafurt, Isabel Munevar, William Mantilla, Ana Cristina Avendaño, Hector Alirio Gonzalez Florez, Paola Jimenez, Javier orlando Pacheco, Paola Pinilla, Ray Manneh Kopp, Juan David Ortiz Diaz, Jesus Insuasty, Marcela Alcala, Angela Barrero, Guillermo Sanchez-Vanegas
Journal: Journal of Clinical Oncology (2022)

e18721 Background: In our experience during the first year of development of ACHOC-C19 study, we observed 26% mortality in patients with cancer and COVID 19 infection. The impact of vaccination was not evaluated prior to the implementation of this strategy worldwide in this kind of population. It was proposed to evaluate the effectiveness of immunization during the second phase of our investigation. Methods: Cohort study derived from the National Registry of Patients with Cancer and COVID-19 (ACHOCC-19). Data were collected from June 2021 since vaccine was available. Patients were: older than 18 years, diagnosed with cancer (solid tumors), treated and/or under follow-up, and with COVID-19 infection. The comparative analysis of the vaccinated and non-vaccinated cohort is presented. Outcomes included: all-cause mortality within 30 days of infection diagnosis, hospitalization, and mechanical ventilation. Effect estimation was performed through relative risk (RR) and multivariate analysis for each event, using generalized linear models of the binomial family. Results: 896 patients were included, 470 were older than 60 years (52.4%) and 59% women (n = 530). 172 patients were recruited in the vaccinated cohort and 724 in the non-vaccinated cohort (ratio: 1 to 4.2). The cumulative incidence of hospitalization among the unvaccinated was 42.4% (n = 307), and among the vaccinated, 29% (n = 50); invasive mechanical ventilation requirement was 8.4% (n = 61) in unvaccinated, and 4.6% (n = 8) in vaccinated. The cumulative incidence of mortality from all causes in the unvaccinated was 17% (n = 123) and in the vaccinated 4.65% (n = 8). Table summarizes the multivariate analysis. The adjusted RR for mortality for the unvaccinated is 3.4 (95% CI: 1.7-6.8), for hospitalization 1.36 (95% CI: 1.08-1.72), and for mechanical ventilation 2.1 (95% CI: 1.02-4.2). Conclusions: The incidence of complications and death in patients with cancer and COVID-19 infection is significantly higher in those who have not received a vaccination schedule compared to those who have been vaccinated. Immunization should be promoted and intensified in this population group.[Table: see text]
EPEN-19. Impact of molecular classification on prognosis in children and adolescents with spinal ependymoma: Results from the HIT-MED database
Authors: Lara Engertsberger, Martin Benesch, Martin Mynarek, Svenja Tonn, Martina Stickan-Verfürth, Angela Funk, Kristian W Pajtler, Beate Timmermann, Rolf-Dieter Kortmann, Torsten Pietsch, Brigitte Bison, Monika Warmuth-Metz, Stefan Rutkowski, Ulrich Schüller
Journal: Neuro-Oncology (2022)

Abstract PURPOSE: Ependymomas of the spinal cord are rare among children, and individual risks of disease progression are difficult to predict. This study aims at evaluating the prognostic impact of DNA methylation-based classification in children with spinal ependymoma. METHODS: Eighty-two patients with spinal ependymoma &amp;lt;22 years registered in the HIT-MED database between 1992 and 2021 were included. Clinical, radiological, and histopathological data were collected retrospectively. DNA methylation profiles of 46 tumors were classified according to the Heidelberg Brain Tumor Classifier. RESULTS: Spinal myxopapillary ependymoma (SP-MPE, n=27) was the most common methylation group followed by spinal ependymoma (SP-EPN, n=15). Two cases belonged to MYCN-amplified subgroup, one had no match, and one was re-classified as anaplastic pilocytic astrocytoma (the latter excluded from final analysis). WHO grade I and III ependymomas (according to the WHO 2016 classification) classified predominantly as SP-MPE, whereas grade II ependymomas clustered into SP-MPE and SP-EPN. 6/15 patients with SP-EPN (40%) suffered from Neurofibromatosis type 2. Among patients with SP-MPE, 23 underwent gross-total and four a subtotal resection (GTR/STR). Relapses of SP-MPE were more common following STR (5-year progression-free survival (5y-PFS) [STR] 25.0% [95% confidence interval: 0.0-68.4], [GTR] 75.0% [53.4-96.6], p=0.003). In the SP-EPN group, 2/8 patients relapsed after STR (5y-PFS 64.3% [22,3-100]) and 0/7 after GTR (n.s.). WHO I° ependymoma had significantly inferior PFS than II° and III° ependymoma (5y-PFS [I°] 39.0% [5.8-62.2], [II°] 82.4% [67.8-97.0], [III°] 50.5% [18.9-82.1], p=0.009). However, PFS did not significantly differ between SP-MPE and SP-EPN (5y-PFS 65.9% [44.9-86.9], 76.9% [46.3-100], respectively). CONCLUSION: Spinal ependymomas of WHO grade I go along with relatively poor PFS in our cohort, while DNA methylation profiling does not segregate patients into distinct risk groups. Still, larger cohorts and further investigations of methylation class heterogeneity in pediatric spinal ependymomas are needed to complete the basis for future clinical decision-making.
Tyrosine kinase inhibitors (TKIs) in trastuzumab emtansine (T-DM1) resistant HER2-positive metastatic breast cancer: A real-world study.
Authors: Yongmei Yin, Chunxiao Sun, Yijia Hua, Mengping Jiang, Fan Yang, Xinyu Wu, Tianyu Zeng, Shengnan Bao, Yan Liang, Xiang Huang, Wei Li
Journal: Journal of Clinical Oncology (2022)

e13029 Background: Trastuzumab emtansine (T-DM1) has shown great effectiveness in treating HER2-positive metastatic breast cancer, but therapies subsequent to T-DM1 progression are still controversial. Here, we investigated efficacy and safety of tyrosine kinase inhibitors (TKIs) based therapy in T-DM1 resistant HER2-positive metastatic breast cancer. Methods: From August 2019 to February 2022, 53 HER2-positive metastatic breast cancer patients received TKIs-based therapy after T-DM1 progression in Jiangsu Province Hospital. We reported progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety profiles of TKIs in treating T-DM1 resistant HER2-positive metastatic breast cancer. Results: 53 patients received TKIs-based therapies as a second or later line therapy. 51 (96.2%) patients received a combined therapy, including TKIs plus capecitabine, vinorelbine or trastuzumab. 2 (3.7%) patients received TKIs alone. The median follow-up time was 19.7 months (95%CI 14.829-24.571). The median PFS was 10.6 months (95%CI 5.530-15.670). OS has not reached. ORR was 18.9% and CBR was 72.5%. For patients who had brain metastasis (n = 12), the median PFS was 10.5 months (95%CI 7.406-13.594) and intracranial ORR was 33.3%. Compared with lapatinib (n = 30), pyrotinib (n = 21) provided a better PFS, but no significant difference was observed (8.0 months vs. 19.0 months, P = 0.076). The most common adverse events were thrombocytopenia (12, 22.6%), hand-foot syndrome (11, 20.8%) and diarrhea (6, 11.3%). Conclusions: TKIs-based therapy could improve the survival of T-DM1 resistant HER2-positive metastatic breast cancer patients, including those with brain metastasis. This provides a novel therapeutic option for HER2-positive breast cancer treatments.
Targeted alpha-emitter therapy with <sup>212</sup>Pb-DOTAMTATE in neuroendocrine tumor subjects who progressed following prior <sup>177</sup>Lu/<sup>90</sup>Y-PRRT.
Authors: Ebrahim Delpassand, Rouzbeh Esfandiari, Izabela Tworowska, Julien Torgue, Jason Daniel Hurt, Rodolfo Nunez
Journal: Journal of Clinical Oncology (2022)

4128 Background: Targeted Alpha-Emitter Therapy (TAT) with 212 Pb-DOTAMTATE has been shown to be safe and effective in subjects with neuroendocrine tumors (NET) who have not received previous PRRT, however, data is lacking for the use of TAT once progression occurs. Herein, we present the safety and efficacy of 212 Pb-DOTAMTATE in subjects with recurrent NETs following prior 177 Lu/ 90 Y-PRRT. Methods: Subjects with biopsy-proven unresectable or metastatic SSTR expressing NETs from different primary sites with at least one measurable lesion who had received progressed after receiving prior PRRT were enrolled and received up to four 8-week cycles of 212 Pb-DOTAMTATE at 67.6 μCi/kg/cycle. Response to treatment was measured per RECIST 1.1 criteria and by 68 Ga/ 64 Cu-DOTATATE PET/CT. Safety parameters were also obtained. Results: A total of 11 PRRT subjects were enrolled regardless of primary tumor location (pancreas (4), small bowel (3), midgut (1), ileum (1), thymus (1), and lung (1)). 8/11 subjects (73%) completed all four cycles. The mean cumulative dose was 20.9 mCi. As of January 2022, an objective radiological response (ORR) was demonstrated in 30% of evaluable subjects (1CR, 2PR, and 7 SD). In addition, 70% (7/10) evaluable subjects demonstrated a response per 68 Ga/ 64 Cu-DOTATATE PET/CT SSTR imaging. One hundred forty-five AEs were reported, with Grade 1 (79%). There were 23 (16%) Grade 2 AEs and 5 (3%) Grade 3/ 4 AEs. Of the AEs reported, 84 (58%) were considered possibly related, and 61 (42%) were considered not related or unlikely related. The most frequent AEs (reported in ≥ 4 subjects) include: alopecia (100%), fatigue (100%), nausea (91%), anemia (36%), alanine aminotransferase increased (36%), aspartate aminotransferase increased (36%) and lymphopenia (46%). Three SAEs were reported (achalasia, asthma exacerbation, and septic shock) one of which resulted in the death of the subject (septic shock). No SAEs were considered related to study drug. Conclusions: This is the first clinical trial of 212 Pb-targeted alpha-emitter therapy in subjects with NETs who progressed following prior PRRT. The use of 212 Pb-DOTAMTATE in the recurrent setting is highly effective with manageable toxicity and warrants further investigation. Clinical trial information: NCT03466216.